Erythropoiesis (production of red cells)

Red cells are produced continuously in the marrow of certain bones. As stated above, in adults the principal sites are the marrow spaces of the vertebrae, ribs, breastbone, and pelvis.Within the bone marrow the red cell is derived from a primitive precursor, or erythroblast, a nucleated cell in which there is no hemoglobin. Proliferation occurs as a result of several successive cell divisions. During maturation hemoglobin appears in the cell, and the nucleus becomes progressively smaller. After a few days the cell loses its nucleus and is then introduced into the bloodstream in the vascular channels of the marrow. Almost 1 percent of the red cells are generated each day, and the balance between red cell production and the removal of aging red cells from the circulation is precisely maintained. If blood is lost from the circulation, the erythropoietic activity of marrow increases until the normal number of circulating cells has been restored.

In a normal adult the red cells of about half a litre (almost one pint) of blood are produced by the bone marrow every week. A number of nutrient substances are required for this process. Some nutrients are the building blocks of which the red cells are composed. For example, amino acids are needed in abundance for the construction of the proteins of the red cell, in particular of hemoglobin. Iron also is a necessary component of hemoglobin. Approximately one-quarter of a gram of iron is needed for the production of a pint of blood. Other substances, required in trace amounts, are needed to catalyze the chemical reactions by which red cells are produced. Important among these are several vitamins, riboflavin, vitaminB12, and folic acid, necessary for the maturation of the developing red cell; and pyridoxine (vitamin B6), required for the synthesis of hemoglobin. The secretions of several endocrine glands influence red cell production. If there is an inadequate supply of thyroid hormone, erythropoiesis is retarded and anemia appears. The male sex hormone, testosterone, stimulates red cell production; for this reason, red cell counts of men are higher than those of women.

The capacity of the bone marrow to produce red cells is enormous. When stimulated to peak activity and when provided adequately with nutrient substances, the marrow can compensatefor the loss of several pints of blood per week. Hemorrhage or accelerated destruction of red cells leads to enhanced marrow activity. The marrow can increase its production of red cells up to eight times the usual rate. After that, if blood loss continues, anemia develops. The rateof erythropoiesis is sensitive to the oxygen tension of the arterial blood. When oxygen tension falls, more red cells are produced and the red cell count rises. For this reason, personswho live at high altitude have higher red cell counts than those who live at sea level. There is a small but significant difference between average red cell counts of persons living in New York City, at sea level pressure, and persons living in Denver, Colo., one mile above sea level, where the atmospheric pressure is lower. Natives of the Andes, living nearly three miles above sea level, have extremely high red cell counts.

The rate of production of erythrocytes is controlled by a hormone (erythropoietin) that is produced largely in the kidneys. When the number of circulating red cells decreases or when the oxygen transported by the blood diminishes, an unidentified sensor detects the change and the production of erythropoietin is increased. This substance is then transported through the plasma to the bone marrow, where it accelerates the production of red cells. The erythropoietin mechanism operates like a thermostat, increasing or decreasing the rate of red cell production in accordance with need. When a person who has lived at high altitude moves to a sea level environment, production of erythropoietin is suppressed, the rate of red cell production declines, and the red cell count falls until the normal sea level value is achieved. With the loss of one pint of blood, the erythropoietin mechanism is activated, red cell production is enhanced, and within a few weeks the number of circulating red cells has been restored to the normal value. The precision of control is extraordinary, so that the number of new red cells produced accurately compensates for the number of cells lost or destroyed. Erythropoietin has been produced in vitro (outside the body) by the technique of genetic engineering (recombinant DNA). The purified, recombinant hormone has promise for persons with chronic renal failure, who develop anemia because of a lack of erythropoietin.